Introduction

This report is the second volume in the series Acute Exposure Guideline Levels for Selected Airborne Chemicals.

In the Bhopal disaster of 1984, approximately 2,000 residents living near a chemical plant were killed and 20,000 more suffered irreversible damage to their eyes and lungs following accidental release of methyl isocyanate. The toll was particularly high because the community had little idea what chemicals were being used at the plant, how dangerous they might be, and what steps to take in case of emergency. This tragedy served to focus international attention on the need for governments to identify hazardous substances and to assist local communities in planning how to deal with emergency exposures.

In the United States, the Superfund Amendments and Reauthorization Act (SARA) of 1986 required that the U.S. Environmental Protection Agency (EPA) identify extremely hazardous substances (EHSs) and, in cooperation with the Federal Emergency Management Agency and the Department of Transportation, assist Local Emergency Planning Committees (LEPCs) by providing guidance for conducting health-hazard assessments for the development of emergency-response plans for sites where EHSs are produced, stored, transported, or used. SARA also required that the Agency for Toxic Substances and Disease Registry (ATSDR) determine whether chemical substances identified at hazardous waste sites or in the environment present a public-health concern.

As a first step in assisting the LEPCs, EPA identified approximately 400 EHSs largely on the basis of their “immediately dangerous to life and health” (IDLH) values developed by the National Institute for Occupational Safety

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Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 2
Introduction
This report is the second volume in the series Acute Exposure Guideline Levels for Selected Airborne Chemicals.
In the Bhopal disaster of 1984, approximately 2,000 residents living near a chemical plant were killed and 20,000 more suffered irreversible damage to their eyes and lungs following accidental release of methyl isocyanate. The toll was particularly high because the community had little idea what chemicals were being used at the plant, how dangerous they might be, and what steps to take in case of emergency. This tragedy served to focus international attention on the need for governments to identify hazardous substances and to assist local communities in planning how to deal with emergency exposures.
In the United States, the Superfund Amendments and Reauthorization Act (SARA) of 1986 required that the U.S. Environmental Protection Agency (EPA) identify extremely hazardous substances (EHSs) and, in cooperation with the Federal Emergency Management Agency and the Department of Transportation, assist Local Emergency Planning Committees (LEPCs) by providing guidance for conducting health-hazard assessments for the development of emergency-response plans for sites where EHSs are produced, stored, transported, or used. SARA also required that the Agency for Toxic Substances and Disease Registry (ATSDR) determine whether chemical substances identified at hazardous waste sites or in the environment present a public-health concern.
As a first step in assisting the LEPCs, EPA identified approximately 400 EHSs largely on the basis of their “immediately dangerous to life and health” (IDLH) values developed by the National Institute for Occupational Safety

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Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 2
and Health (NIOSH) in experimental animals. Although several public and private groups, such as the Occupational Safety and Health Administration (OSHA) and the American Conference of Governmental Industrial Hygienists (ACGIH), have established exposure limits for some substances and some exposures (e.g., workplace or ambient air quality), these limits are not easily or directly translated into emergency exposure limits for exposures at high levels but of short duration, usually less than 1 h, and only once in a lifetime for the general population, which includes infants, children, the elderly, and persons with diseases, such as asthma, heart disease, or lung disease.
The National Research Council (NRC) Committee on Toxicology (COT) has published many reports on emergency exposure guidance levels and spacecraft maximum allowable concentrations for chemicals used by the Department of Defense (DOD) and the National Aeronautics and Space Administration (NASA) (NRC 1968, 1972, 1984a,b,c,d, 1985a,b, 1986a,b, 1987, 1988, 1994, 1996a,b, 2000). COT has also published guidelines for developing emergency exposure guidance levels for military personnel and for astronauts (NRC 1986b, 1992). Because of COT’s experience in recommending emergency exposure levels for short-term exposures, in 1991 EPA and ATSDR requested that COT develop criteria and methods for developing emergency exposure levels for EHSs for the general population. In response to that request, the NRC assigned this project to the COT Subcommittee on Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances. The report of that subcommittee, Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances (NRC 1993), provides step-by-step guidance for setting emergency exposure levels for EHSs. Guidance is given on what data are needed, what data are available, how to evaluate the data, and how to present the results.
In November l995, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC)1 was established to identify, review, and interpret relevant toxicologic and other scientific data and to develop acute exposure guideline levels (AEGLs) for high-priority, acutely toxic chemicals. The NRC’s previous name for acute exposure levels—community emergency exposure levels (CEELs)—was replaced by the term AEGLs to reflect the broad application of these values to planning,
1
NAC is composed of members from EPA, DOD, many other federal and state agencies, industry, academia, and other organizations. The roster of NAC is shown on page 8.

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Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 2
response, and prevention in the community, the workplace, transportation, the military, and the remediation of Superfund sites.
AEGLs represent threshold exposure limits (exposure levels below which adverse health effects are not likely to occur) for the general public and are applicable to emergency exposures ranging from 10 min to 8 h. Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 min, 30 min, 1 h, 4 h, and 8 h) and are distinguished by varying degrees of severity of toxic effects.
The three AEGLs are defined as follows:
AEGL-1 is the airborne concentration (expressed as ppm [parts per million] or mg/m3 [milligrams per cubic meter]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic nonsensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.
AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape.
AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening health effects or death.
Airborne concentrations below AEGL-1 represent exposure levels that can produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsensory adverse effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent threshold levels for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to unique or idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL.

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Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 2
SUMMARY OF REPORT ON GUIDELINES FOR DEVELOPING AEGLS
As described in the Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances (NRC 1993) and the NAC guidelines report Standing Operating Procedures on Acute Exposure Guideline Levels for Hazardous Substances (NRC 2001), the first step in establishing AEGLs for a chemical is to collect and review all relevant published and unpublished information available on a chemical. Various types of evidence are assessed in establishing AEGL values for a chemical. These include information from (1) chemical-physical characterizations, (2) structure-activity relationships, (3) in vitro toxicity studies, (4) animal toxicity studies, (5) controlled human studies, (6) observations of humans involved in chemical accidents, and (7) epidemiologic studies. Toxicity data from human studies are most applicable and are used when available in preference to data from animal studies and in vitro studies. Toxicity data from inhalation exposures are most useful for setting AEGLs for airborne chemicals because inhalation is the most likely route of exposure and because extrapolation of data from other routes would lead to additional uncertainty in the AEGL estimate.
For most chemicals, actual human toxicity data are not available or critical information on exposure is lacking, so toxicity data from studies conducted in laboratory animals are extrapolated to estimate the potential toxicity in humans. Such extrapolation requires experienced scientific judgment. The toxicity data from animal species most representative of humans in terms of pharmacodynamic and pharmacokinetic properties are used for determining AEGLs. If data are not available on the species that best represents humans, the data from the most sensitive animal species are used to set AEGLs. Uncertainty factors are commonly used when animal data are used to estimate minimal risk levels for humans. The magnitude of uncertainty factors depends on the quality of the animal data used to determine the no-observed-adverseeffect level (NOAEL) and the mode of action of the substance in question. When available, pharmacokinetic data on tissue doses are considered for interspecies extrapolation.
For substances that affect several organ systems or have multiple effects, all end points—including reproductive (in both sexes), developmental, neurotoxic, respiratory, and other organ-related effects—are evaluated, the most important or most sensitive effect receiving the greatest attention. For carcinogenic chemicals, theoretical excess carcinogenic risk is estimated, and the AEGLs corresponding to carcinogenic risks of 1 in 10,000 (1×10–4), 1 in

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Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 2
100,000 (1×10−5), and 1 in 1,000,000 (1×10−6) exposed persons are estimated.
REVIEW OF AEGL REPORTS
As NAC began developing chemical-specific AEGL reports, EPA and DOD asked the NRC to review independently the NAC reports for their scientific validity, completeness, and consistency with the NRC guideline reports (NRC 1993; NRC in press). The NRC assigned this project to the COT Subcommittee on Acute Exposure Guideline Levels. The subcommittee has expertise in toxicology, epidemiology, pharmacology, medicine, industrial hygiene, biostatistics, risk assessment, and risk communication.
The AEGL draft reports are initially prepared by ad hoc AEGL Development Teams consisting of a chemical manager, two chemical reviewers, and a staff scientist of the NAC contractor—Oak Ridge National Laboratory. The draft documents are then reviewed by NAC and elevated from “draft” to “proposed” status. After the AEGL documents are approved by NAC, they are published in the Federal Register for public comment. The reports are then revised by NAC in response to the public comments, elevated from “proposed” to “interim” status, and sent to the NRC Subcommittee on Acute Exposure Guideline Levels for final evaluation.
The NRC subcommittee’s review of the AEGL reports prepared by NAC and its contractors involves oral and written presentations to the subcommittee by the authors of the reports. The NRC subcommittee provides advice and recommendations for revisions to ensure scientific validity and consistency with the NRC guideline reports (NRC 1993, 2001). The revised reports are presented at subsequent meetings until the subcommittee is satisfied with the reviews.
Because of the enormous amount of data presented in the AEGL reports, the NRC subcommittee cannot verify all the data used by NAC. The NRC subcommittee relies on NAC for the accuracy and completeness of the toxicity data cited in the AEGLs reports.
This report is the second volume in the series Acute Exposure Guideline Levels for Selected Airborne Chemicals. AEGL reports for aniline, arsine, monomethylhydrazine, and dimethylhydrazine were reviewed in the first volume. AEGL documents for five chemicals—phosgene, propylene glycol dinitrate, 1,1,1,2-tetrafluoroethane, 1,1-dichloro-1-fluoroethane, and hydrogen cyanide—are published as an appendix to this report. The subcommittee